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Eur J Neurol. 2016 Jan;23(1):45-52. doi: 10.1111/ene.12664. Epub 2015 Feb 9.

Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis.

Author information

1
Neurologia I, Istituto Neurologico Carlo Besta, Milano, Italy.
2
Neurologia II, Seconda Università di Napoli, Napoli, Italy.
3
Dipartimento di Neurologia, Centro Regionale SLA, AOUP 'P Giaccone', Università di Palermo, Palermo, Italy.
4
NeuroCenter, Istituto Clinico Humanitas, Milano; Istituto di Neurologia, Università Cattolica del Sacro Cuore, Milano, Italy.

Erratum in

Abstract

BACKGROUND AND PURPOSE:

Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid that is produced in the liver and used for treatment of chronic cholestatic liver diseases. Experimental studies suggest that TUDCA may have cytoprotective and anti-apoptotic action, with potential neuroprotective activity. A proof of principle approach was adopted to provide preliminary data regarding the efficacy and tolerability of TUDCA in a series of patients with amyotrophic lateral sclerosis (ALS).

METHODS:

As a proof of principle, using a double-blind placebo controlled design, 34 ALS patients under treatment with riluzole who were randomized to placebo or TUDCA (1 g twice daily for 54 weeks) were evaluated after a lead-in period of 3 months. The patients were examined every 6 weeks. The primary outcome was the proportion of responders [those subjects with improvement of at least 15% in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) slope during the treatment period compared to the lead-in phase]. Secondary outcomes included between-treatment comparison of ALSFRS-R at study end, comparison of the linear regression slopes for ALSFFRS-R mean scores and the occurrence of adverse events.

RESULTS:

Tauroursodeoxycholic acid was well tolerated; there were no between-group differences for adverse events. The proportion of responders was higher under TUDCA (87%) than under placebo (P = 0.021; 43%). At study end baseline-adjusted ALSFRS-R was significantly higher (P = 0.007) in TUDCA than in placebo groups. Comparison of the slopes of regression analysis showed slower progression in the TUDCA than in the placebo group (P < 0.01).

CONCLUSIONS:

This pilot study provides preliminary clinical data indicating that TUDCA is safe and may be effective in ALS.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00877604.

KEYWORDS:

amyotrophic lateral sclerosis; cholic acids; tauroursodeoxycholic acid

PMID:
25664595
PMCID:
PMC5024041
DOI:
10.1111/ene.12664
[Indexed for MEDLINE]
Free PMC Article

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